The balance between excitation and inhibition in the brain is important for proper function and is maintained by two major classes of neurons: excitatory projection neurons and inhibitory local circuit interneurons. While excitation is primarily mediated by the neurotransmitter glutamate, GABA primarily mediates inhibition. Recently, multiple regulatory roles of GABAergic interneurons have been identified (Di Cristo, 2007). GABAergic interneurons regulate neuronal proliferation, migration and differentiation during development, as well as excitability, temporal synchrony and refinement of local cortical circuits. The dysfunction of GABA-regulated circuits has been implicated in different psychiatric disorders such as schizophrenia, autism, and Tourette's syndrome, as well as epilepsy (Blatt et al. 2001; Casanova et al. 2002; Cossette et al., 2002; DiCicco-Bloom et al. 2006; Ma et al. 2005; Noebels, 2003). In methyl CpG-binding protein (Mecp2) mutant mice (Bienvenu and Chelly, 2006; Chahrour and Zoghbi, 2007; Moretti and Zoghbi, 2006), a model for the human autism spectrum disorder (ASD) Rett syndrome, GABA-dependent inhibitory cortical activity decreases (Dani et al. 2005). In dorsal lateral prefrontal cortex of schizophrenic patients, one of the most consistent findings is a reduction in GAD67, the enzyme responsible for GABA synthesis (Lewis et al. 2005). Therefore, multiple lines of evidence implicate alterations of GABAergic function in a variety of neurological diseases.
Yet, despite this knowledge of brain function, there remains a need for the development of animal models for the discovery of therapeutic agents for use in preventing or treating such neurological diseases.